The Role of Efferocytosis in Inflammatory Arthritis

胞吞作用在炎症性关节炎中的作用

基本信息

  • 批准号:
    10572853
  • 负责人:
  • 金额:
    $ 24.23万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-02-14 至 2025-01-31
  • 项目状态:
    未结题

项目摘要

THE ROLE OF EFFEROCYTOSIS IN INFLAMMATORY ARTHRITIS Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints which affects 1 in 100 people globally and millions in the US alone. We noted marked presence of apoptotic cells in the inflamed joints of arthritic mice. Apoptosis is intricately linked with phagocytosis of apoptotic cells, also known as ‘efferocytosis’. The current dogma suggests that increased apoptotic cell persistence in tissues inevitably leads to pathology. However, our data presented in this application suggest that this dogma warrants further testing. First, we show that systemic injection of apoptotic cells effectively alleviates inflammation in arthritic mice. Further, cell-free apoptotic cell supernatants or even purified apoptotic cell-released metabolites potently suppress inflammatory arthritis. Finally, pharmacologic or genetic efferocytosis reduction (not complete ablation) also reduce inflammation in arthritic mice. Here, we will test the hypothesis that reduced efferocytosis alleviates inflammation in arthritis through increased release of anti-inflammatory mediators (from uncleared apoptotic cells) and enhanced corpse processing/degradation (due to reduced corpse load in phagocytes). We will pursue the following aims: 1. Using mice with pharmacologic or genetic decrease in efferocytosis, we will quantify multiple disease parameters in arthritis, determine the numbers of apoptotic cells in the inflamed joints, analyze the phagocyte response, and analyze the metabolomics of reduced cell clearance environments. 2. Generate and validate a new transgenic mouse model with tissue-specific, inducible reduction of efferocytosis. Our findings will further our understanding of efferocytosis in homeostasis and inflammation and could open new avenues in therapeutic designs for the treatment of rheumatoid arthritis.
淋巴细胞增生在炎性关节炎中的作用

项目成果

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Sanja Arandjelovic其他文献

Sanja Arandjelovic的其他文献

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{{ truncateString('Sanja Arandjelovic', 18)}}的其他基金

Impact of phagocytosis on amyloid beta-induced pathology
吞噬作用对β淀粉样蛋白诱导的病理学的影响
  • 批准号:
    10724363
  • 财政年份:
    2023
  • 资助金额:
    $ 24.23万
  • 项目类别:
Understanding A Molecular Cascade That Drives Neutrophil Mediated Pathology In Arthritis
了解驱动中性粒细胞介导的关节炎病理学的分子级联
  • 批准号:
    10658202
  • 财政年份:
    2023
  • 资助金额:
    $ 24.23万
  • 项目类别:

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